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      Metallothioneins (I+II) and thyroid–thymus axis efficiency in old mice: role of corticosterone and zinc supply


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          Thymic atrophy or thymus absence causes depressed thyroid–thymus axis (TTA) efficiency in old, young propyl-thiouracil (PTU) (experimental hypothyroidism) and in young-adult thymectomised (Tx) mice, respectively. Altered zinc turnover may be also involved in depressed TTA efficiency. Zinc turnover is under the control of zinc-bound metallothioneins (Zn-MTs) synthesis. Thyroid hormones, corticosterone and nutritional zinc affect Zn-MT induction. Zn-MT releases zinc in young-adult age during transient oxidative stress for prompt immune response. In constant oxidative stress (ageing and liver regeneration after partial hepatectomy), high liver Zn-MTs, low zinc ion bioavailability and depressed TTA efficiency appear. This last finding suggested that MT might not release zinc during constant oxidative stress leading to impaired TTA efficiency. The aim of this work/study is to clarify the role of Zn-MTs (I+II) in TTA efficiency during development and ageing. The main results are (1) Old and PTU mice display high corticosterone, enhanced liver MTmRNA, low zinc and depressed TTA efficiency restored by zinc supply. Increased survival and no significant increments in basal liver Zn-MTs proteins occur in old and PTU mice after zinc supply. (2) Lot of zinc ions bound with MT in the liver from old mice than young (HPLC). (3) Young-adult Tx mice, evaluated at 15 days from thymectomy, display high MTmRNA and nutritional–endocrine–immune damage restored by zinc supply or by thymus grafts from old zinc-treated mice. (4) Young-adult Tx mice, but evaluated at 40 days from thymectomy, display natural normalisation in MTmRNA and nutritional–endocrine–immune profile with survival similar to normal mice. (5) Stressed (constant dark for 10 days) mice overexpressing MT display low zinc, depressed immunity, reduced thymic cortex, high corticosterone, altered thyroid hormones turnover showing a likeness with old mice. These findings, taken altogether, show that corticosterone is pivotal in MTs induction under stress. MTs bind preferentially zinc ions in constant oxidative stress, but with no release of zinc from MT leading to impaired TTA efficiency. Zinc supply restores the defect because zinc has no interference in affecting pre-existing Zn-MTs protein concentrations in old and PTU mice. Therefore, free zinc ions are available for TTA efficiency after zinc supply. Thymus from old zinc-treated mice induces the same restoring effect when transplanted in Tx recipients. However, Tx mice display natural normalisation in MTmRNA and in nutritional–endocrine–immune profile in the long run. Therefore, Zn-MTs (I+II) are crucial in zinc homeostasis for endocrine–immune efficiency during the entire life assuming a role of potential and novel ‘biological clock of ageing’.

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          • Record: found
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          Increased cytokine production in mononuclear cells of healthy elderly people.

          The production of cytokines during aging, except interleukin (IL)-2, has been neglected in humans. We measured the in vitro production of IL-6, tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma and IL-1 beta by peripheral mononuclear cells from selected healthy young (mean age 26.8 years) and aged (mean age 80.2 years) subjects. Significant increases of IL-6, TNF-alpha and IL-1 beta levels were found in mitogen-stimulated cultures from aged donors, occurring at 24 to 72 h after stimulation. No significant differences were observed for IFN-gamma production. Proliferative capability of cells stimulated with PHA was not impaired in aged subjects. Since the amounts of all cytokines studied were similar in unstimulated cultures from young and aged subjects, and also serum levels of TNF-alpha did not differ, these data indicate that the cellular machinery for the production of these cytokines is well preserved in aging, and also that cells from old people are able to up-regulate their production in response to appropriate stimuli. The increases in cytokine synthesis were not dependent on changes in the number of monocytes, nor were they related to the significant rise of CD45RO+, and the concomitant decrease of CD45RA+, occurring in both CD4+ and CD8+ lymphocytes from aged subjects. The increased production of pro-inflammatory cytokines by stimulated mononuclear cells of healthy aged subjects may be relevant to several aspects of age-associated pathological events, including atherosclerosis, osteoporosis, fibrosis and dementia.
            • Record: found
            • Abstract: not found
            • Article: not found


            Dean Hamer (1986)
              • Record: found
              • Abstract: found
              • Article: not found

              Effects of stress on the immune system.

              Stress, distress and a variety of psychiatric illnesses, notably the affective disorders, are increasingly reported to be associated with immunosuppression. The concept that psychic distress may predispose to medical illness is centuries old but has only recently attracted the attention of the scientific community at large. Interdisciplinary collaboration has established psychoneuroimmunology, or neuroimmunomodulation, as a new field of investigation with the goal of rigorous scientific research into the elusive mind-body connection. This has resulted in the rapid accumulation of information which falls across the boundary lines of psychiatry, immunology, neurosciences and endocrinology. Here David Khansari, Anthony Murgo and Robert Faith review the effects of stress on the endocrine and central nervous systems and the interactions between these systems and the immune response after exposure to stress signals.

                Author and article information

                Mech Ageing Dev
                Mech. Ageing Dev
                Mechanisms of Ageing and Development
                Elsevier Science Ireland Ltd.
                9 February 2002
                31 March 2002
                9 February 2002
                : 123
                : 6
                : 675-694
                [a ]Section: Nutrition, Immunity and Ageing, Immunology Centre, Research Department of Gerontology and Geriatrics ‘Nino Masera’, Italian National Research Centre on Ageing (I.N.R.C.A.), Via Birarelli 8, 60121 Ancona, Italy
                [b ]Biochemical Institute, Veterinary Faculty, University of Bologna, Bologna, Italy
                Author notes
                [* ]Corresponding author. Tel.: +39-71-8004216; fax: +39-71-206791 e.mocchegiani@ 123456inrca.it
                Copyright © 2002 Elsevier Science Ireland Ltd. All rights reserved.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                : 6 August 2001
                : 31 October 2001
                : 22 November 2001

                Developmental biology
                zinc,metallothioneins,ageing,inflammation,thyroid–thymus axis,corticosterone,thymus grafts,ptu,stress,mts transgenic mice,biological clock,survival,at, active thymulin,mts, metallothioneins,mt-i*, metallothioneins overexpressing mice,ptu, propyl-thiouracil,tecs, thymic epithelial cells,tsh, thyroid stimulating hormone,tta, thyroid–thymus axis,tt, total thymulin,tx, thymectomy


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